Modulating Both Tumor Cell Death and Innate Immunity Is Essential for Improving Radiation Therapy Effectiveness

Area of Science:

• Oncology
• Immunology
• Radiation Biology

Background:

• Radiation therapy is a primary cancer treatment modality.
• Ionizing radiation (IR) induces DNA damage, leading to various cancer cell death pathways (apoptosis, necrosis, autophagy, mitotic catastrophe) and cellular senescence.
• IR significantly influences tumor-infiltrating immune cells, affecting treatment outcomes.

Purpose of the Study:

• To review cell death modalities induced by IR.
• To summarize the immunogenic properties of irradiated cancer cells.
• To discuss the effects of IR on innate immune cells (dendritic cells, macrophages, NK cells) and their therapeutic potential.

Main Methods:

• Literature review of preclinical and clinical studies.
• Analysis of the interplay between radiation therapy and the immune system.
• Focus on innate immune cell functions and their response to IR.

Main Results:

• IR triggers diverse cancer cell death mechanisms and senescence.
• Irradiated cancer cells exhibit immunogenic properties.
• IR modulates innate immune cell functions, particularly dendritic cells, macrophages, and NK cells.

Conclusions:

• IR's complex interaction with the immune system is crucial for cancer treatment.
• Understanding these interactions can optimize combination therapies, such as radiation with immune checkpoint blockade.
• Targeting IR-modulated immune responses holds promise for novel cancer therapies.